Integrative Analysis of lncRNA–RBP (RNA-Binding Protein) Regulatory Networks Reveals Molecular Targets for Enhancing Zea mays Resistance to Aspergillus flavus and Aflatoxin Contamination

<i>Aspergillus flavus</i> infection and accumulation of carcinogenic aflatoxins are detrimental to maize (<i>Zea mays</i>) production and consumption. We investigated lncRNA-RBP interactions during maize-<i>A. flavus</i> crosstalk using transcriptomic profiling, structural analysis, molecular docking simulations, and machine learning approaches. Analysis of 18 RNA-seq datasets identified 2104 lncRNAs in maize, of which 461 were differentially expressed under <i>A. flavus</i> infection. Distinct lncRNAs were preferentially induced under infection (e.g., <i>Zm00001eb303170</i>) or normal germination (e.g., <i>Zm00001eb144150</i>, <i>Zm00001eb406410</i>). RNA secondary structure predictions indicated high structural heterogeneity and thermodynamic stability, consistent with dynamic regulatory potential. Docking simulations with six key RNA binding proteins (RBPs)-including branch point bridging protein (BPB), KH domain protein, and pentatricopeptide repeat (PPR) proteins-demonstrated strong lncRNA-protein binding, with the lncRNA1-BPB complex exhibiting the highest binding affinity. ML algorithms identified the crucial role of tryptophan in determining interactions, while lncRNA17-KH and lncRNA1-BP complexes were found to have the best interaction under normal germination and <i>A. flavus</i> infection, respectively. The lncRNA-miRNA-mRNA regulatory network highlighted lncRNAs functioning as decoys or precursors of stress-responsive miRNAs (e.g., zma-miR156, zma-miR164, zma-miR399). These interactions targeted transcriptional regulators, splicing factors, and metabolic enzymes implicated in stress tolerance, seed germination, and systemic acquired resistance. The maize lncRNAs are active regulatory molecules embedded in complex RBP and miRNA interaction networks that fine-tune gene expression during <i>A. flavus</i> infection. The study provides novel insights into lncRNA-mediated resistance mechanisms and offers potential molecular targets for breeding or gene editing to mitigate aflatoxin contamination.